β2-adrenoceptors are essential for desipramine, venlafaxine or reboxetine action in neuropathic pain

Yalçın, İpek; Tessier, Luc-Henri; Petit-Demoulière, Nathalie; Doridot, Stéphane; Hein, Lutz; Freund-Mercier, Marie José; Barrot, Michel

doi:10.1016/j.nbd.2008.11.003

Cited by 73 publications

(84 citation statements)

References 57 publications

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“…In this model, the tricyclic antidepressant drug nortriptyline (5 mg/kg, intraperitoneal, twice a day) relieves the neuropathic allodynia after around 2 weeks of treatment, as illustrated in Figure 2 (F7,91=15.3, p<0.001; post-hoc: (CuffNor=Sham)>CuffSal at p<0.001 on days 29 -34). At this dose, no acute analgesic action of the antidepressant is observed 16,17 . To mimic the lasting pain relief that is present in patients taking such drugs, the mice can be tested before the morning drug administration rather than after.…”

Section: Representative Resultsmentioning

confidence: 86%

“…Similar to clinical observations: gabapentinoids display both an acute short-lasting analgesic action at high dose and a delayed sustained relieving action that is observed after a few days of treatment, tricyclic antidepressants and selective serotonin and noradrenaline reuptake inhibitors have no acute analgesic effect at relevant dose but they display a delayed sustained relieving action that requires 1 to 2 weeks of treatment, and the selective serotonin reuptake inhibitor fluoxetine is ineffective 16 . The model is thus appropriate to study the molecular mechanism underlying these treatments [16][17][18]44,45,47 , which may reveal new therapeutic targets to test in patients [48][49][50][51] .…”

Section: Discussionmentioning

confidence: 99%

“…The possibility to use genetically modified animals 17,18,[44][45][46][47]52 , the long-lasting allodynia, the response to clinically used treatments and the time-dependent development of anxiodepressive symptoms make this model appropriate for the study of the various aspects and consequences of neuropathic pain and its treatments, which have already brought valuable information to this field of research.…”

Section: Discussionmentioning

confidence: 99%

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The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

Yalçın

Megat

Barthas

et al. 2014

JoVE

Self Cite

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Neuropathic pain arises as a consequence of a lesion or a disease affecting the somatosensory system. This syndrome results from maladaptive changes in injured sensory neurons and along the entire nociceptive pathway within the central nervous system. It is usually chronic and challenging to treat. In order to study neuropathic pain and its treatments, different models have been developed in rodents. These models derive from known etiologies, thus reproducing peripheral nerve injuries, central injuries, and metabolic-, infectious-or chemotherapy-related neuropathies. Murine models of peripheral nerve injury often target the sciatic nerve which is easy to access and allows nociceptive tests on the hind paw. These models rely on a compression and/or a section. Here, the detailed surgery procedure for the "cuff model" of neuropathic pain in mice is described. In this model, a cuff of PE-20 polyethylene tubing of standardized length (2 mm) is unilaterally implanted around the main branch of the sciatic nerve. It induces a long-lasting mechanical allodynia, i.e., a nociceptive response to a normally non-nociceptive stimulus that can be evaluated by using von Frey filaments. Besides the detailed surgery and testing procedures, the interest of this model for the study of neuropathic pain mechanism, for the study of neuropathic pain sensory and anxiodepressive aspects, and for the study of neuropathic pain treatments are also discussed.

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Section: Representative Resultsmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

Yalçın

Megat

Barthas

et al. 2014

JoVE

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“…Several preclinical studies have shown that DMI has antiallodynic properties in models of neuropathic pain (34)(35)(36)(37). The DMI dose-response may vary between genetic backgrounds, neuropathic pain models, and type of Von Frey hair, but overall, chronic DMI administration promotes antiallodynic responses in rodents.…”

Section: Discussionmentioning

confidence: 99%

RGS9-2–controlled adaptations in the striatum determine the onset of action and efficacy of antidepressants in neuropathic pain states

Mitsi

Terzi

Purushothaman

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The striatal protein Regulator of G-protein signaling 9-2 (RGS9-2) plays a key modulatory role in opioid, monoamine, and other G-protein-coupled receptor responses. Here, we use the murine spared-nerve injury model of neuropathic pain to investigate the mechanism by which RGS9-2 in the nucleus accumbens (NAc), a brain region involved in mood, reward, and motivation, modulates the actions of tricyclic antidepressants (TCAs). Prevention of RGS9-2 action in the NAc increases the efficacy of the TCA desipramine and dramatically accelerates its onset of action. By controlling the activation of effector molecules by G protein α and βγ subunits, RGS9-2 affects several protein interactions, phosphoprotein levels, and the function of the epigenetic modifier histone deacetylase 5, which are important for TCA responsiveness. Furthermore, information from RNA-sequencing analysis reveals that RGS9-2 in the NAc affects the expression of many genes known to be involved in nociception, analgesia, and antidepressant drug actions. Our findings provide novel information on NAc-specific cellular mechanisms that mediate the actions of TCAs in neuropathic pain states.desipramine | duloxetine | HDAC5 | spared nerve injury | gene expression R egulator of G-protein signaling 9-2 (RGS9-2) is an intracellular modulator of G-protein-coupled receptor (GPCR) function, which is expressed in medium spiny neurons and cholinergic interneurons of the striatum (1, 2). RGS9-2 influences the magnitude and time course of GPCR signaling by promoting GTPase activity of the Gα subunit and by preventing activation of Gα effectors (3). This modulation can also influence the duration of interactions between the Gβγ subunits and their effector molecules. In addition to Gα subunits, RGS9-2 interacts with several scaffolds and signal transduction proteins that affect its function, expression, and cellular localization. Interactions with the Gβ5 subunit and the adaptor protein R7BP determine the stability and cellular localization of RGS9-2, respectively (3, 4). Several recent studies have provided information on the regulation and function of RGS9-2 complexes in the striatum and how these complexes affect pharmacologic responses (2, 5, 6). In particular, RGS9-2 has been shown to modulate the actions of various psychotropic, antiparkinsonian, neuroleptic, and opiate analgesic drugs (1, 7). The nucleus accumbens (NAc) is a striatal brain region that is a major site of antidepressant drug action (8). Recent studies provided information on signal transduction events triggered by tricyclic antidepressants (TCAs) in NAc neurons and identified several second messengers, transcription factors, and epigenetic molecules involved in their therapeutic actions (9-11). TCAs, such as desipramine (DMI) and nortriptyline (NTL), and selective serotonin/norepinephrine reuptake inhibitors (SNRIs) have also been used to treat neuropathic pain, a complex chronic disorder that is highly comorbid with anxiety and depression (12, 13) and is characterized by thermal hyperalgesia, mech...

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“…Another aspect that confirms the close relation between cancer pain and mood depression is the treatment. It is well known that ADs with a broad spectrum of action on norepinephrine (NE) and serotonin (5HT) demonstrate a larger efficacy as compared to selective noradrenergic (NARIs) or selective serotoninergic antidepressants (SSRIs) both on depression and on chronic pain [17]. ADs demonstrate both a fast direct and a late indirect pain-mitigating effect, this latter related to the improvement of mood depression.…”

Section: Introductionmentioning

confidence: 99%

Pain, Depression And Coping Styles: Assessment And Evaluation In Cancer Pain Population

A¹

2013

J Pain Relief

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Cancer patients may suffer from a plethora of symptoms at all stages of their disease. Pain is one of the most feared and distressing symptoms experienced by people with cancer and may be the dominating symptom at time of diagnosis of cancer, a sign of disease relapse, a symptom of late toxicity and a key symptom in patients with advanced cancer. Pain is often associated with depression and impaired quality of life, consistent with a biopsychosocial model. The main goal of this study is to investigate the relation among pain, anxiety and depression in a population of oncological patients and the secondary objective is to analyse the association between cancer pain and coping styles.

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β2-adrenoceptors are essential for desipramine, venlafaxine or reboxetine action in neuropathic pain

Cited by 73 publications

References 57 publications

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

RGS9-2–controlled adaptations in the striatum determine the onset of action and efficacy of antidepressants in neuropathic pain states

Pain, Depression And Coping Styles: Assessment And Evaluation In Cancer Pain Population

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